OBJECTIVE To determine the age of classical MHC class I molecules. RESULTS Here we show that an identical functional MHC class I molecule is present in two different primate species with an approximate divergence time of 0.7 million years. Lymphocytes from the red-crested tamarin (Saguinus geoffroyi) expressed an MHC class I allele (Sage-G*01) that was identical in coding sequence to an MHC class I allele (Saoe-G*08) found in the cotton-top tamarin (Saguinus oedipus). Furthermore, influenza virus-specific cytotoxic T lymphocytes (CTLs) generated in the cotton-top tamarin killed lymphocytes expressing the influenza virus nucleoprotein (NP) from the red-crested tamarin. DISCUSSION The products of the highly polymorphic and variable major histocompatibility complex (MHC) class I loci play a crucial role in host defenses against infectious disease. While similar alleles have been found in closely related species, sharing of a functional MHC class I allele between two species has never been reported. Since the influenza virus NP epitope is bound by Saoe-G*08 in the cotton-top tamarin, it is likely that this molecule is functional in both species. FUTURE DIRECTIONS These data provide the first evidence that functional MHC class I molecules can be maintained entirely intact in two separate species. KEY WORDS MHC class I, Cotton-top tamarin, Influenza, New World Primates, cytotoxic T lymphocytes FUNDING NIH RR00167, DK44886 PUBLICATIONS Evans, DT, Piekarczyk, MS, Hinshaw, VS and D.I. Watkins. 1998. Two different primate species express an identical functional MHC class I allele. Immunogenetics 47:206-211.